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Toxicologic Pathology
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Possible Involvement of bcl-2 Suppression in Wild-Type p53 Gene-Dependent Cell Growth Repression in Rat Osteosarcoma Cells

Kanya Honoki

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

Toshifumi Tsujiuchi

Department of Oncological Pathology, Nara Medical University, Kashihara, Nara, Japan

Masahiro Tsutsumi

Department of Oncological Pathology, Nara Medical University, Kashihara, Nara, Japan

Akira Kido

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

Toru Morishita

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

Masatoshi Yoshimoto

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

Yoshizumi Miyauchi

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

Yoshio Mii

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

Susumu Tamai

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan

Yoichi Konishi

Department of Oncological Pathology, Nara Medical University, Kashihara, Nara, Japan

We recently obtained 3 cloned cell lines demonstrating the p53 mutation from a lung metastatic nodule of a rat transplantable osteosarcoma. In this study, we applied wild-type p53 gene transfer to the rat osteosarcoma cells by lipofection to investigate the effects on cell growth, expression of genes such as waf1/p21, bcl-2, and bax, and nucleosomal DNA fragmentation due to apoptosis. Reconstitution of the p53 gene inhibits cellular growth, and this growth-suppressive effect is partly due to apoptosis involving bcl-2 gene suppression in this tumor type. This rat osteosarcoma model is similar in biologic behavior to human cases and thus is very suitable for further investigation of tumorigenesis and gene therapy for osteosarcoma.

Key Words: Osteosarcoma • rat • p53 • waf1/p21 • bcl-2 • bax • apoptosis

Toxicologic Pathology, Vol. 28, No. 4, 575-579 (2000)
DOI: 10.1177/019262330002800411
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